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BIOMARKER:

KRAS G12V

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Entrez ID:
Related biomarkers:
Related tests:
1m
Oncogenic KRAS mutations modulate BAX-mediated cell death. (PubMed, Biochim Biophys Acta Mol Cell Res)
This suggests a potential mechanism explaining the increased sensitivity of CRC cells harboring a KRAS-activated pathway to acetate. These findings contribute to a clearer understanding of how KRAS regulate BAX function, a relevant aspect in tumor progression.
Journal • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS G13D • RAS wild-type • KRAS G12 • BAX expression • KRAS expression
1m
The Agena iPlex HS Lung Panel on the MassARRAY System Is Able to Robustly Characterize the Molecular Profile of FFPE-Derived Lung Tumor Samples Previously Deemed QNS on Multiple NGS Platforms (AMP 2024)
The Agena iPlex HS Lung Panel on the MassARRAY System is highly tolerant of poor quantity and quality DNA, recovering and delivering accurate results on samples that would otherwise fail NGS-based analysis.
Next-generation sequencing
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • KRAS G12V • KRAS G12 • KRAS G13 • KRAS Q61 • KRAS deletion
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TruSight Oncology 500 Assay
2ms
KRAS inhibitors in drug resistance and potential for combination therapy. (PubMed, Tumori)
Recently, an emergency approval from the US-FDA has been issued for KRASG12C inhibitors (sotorasib and adagrasib) for metastatic lung cancer treatment. Moreover, because KRASG12D and KRASG12V are more common than KRASG12C, focus must be placed on the therapeutic strategies for this type of patient, along with sustained efforts in research on these targets. In the present review, we try to focus on various strategies to overcome rapid resistance through the use of combinational treatments to improve the activity of KRASG12C inhibitors.
Review • Journal • Combination therapy
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KRAS (KRAS proto-oncogene GTPase)
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KRAS G12D • KRAS G12V
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Lumakras (sotorasib) • Krazati (adagrasib)
2ms
KRAS mutations in endometrial cancers: Possible prognostic and treatment implications. (PubMed, Gynecol Oncol)
KRAS-mut represents a genotypically distinct group of ECs. Overlap exists with genomic predictors (TMB-high, MSI-high) of immunotherapy response, suggesting a possible biomarker-driven combination option with immunotherapy. Clinical trials to evaluate these strategies should be developed.
Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability)
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KRAS mutation • BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS overexpression • HER-2 positive + RAS wild-type
2ms
KRAS G12C mutation in NSCLC in a small genetic center: insights into sotorasib therapy response potential. (PubMed, Sci Rep)
Notably, patients harboring the G12C variant responded favorably to sotorasib medication. These results underscore the importance of mutational profiling and targeted therapeutic approaches in managing NSCLC, particularly highlighting the promising efficacy of sotorasib in G12C-mutated cases.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12
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Archer® FusionPlex® Comprehensive Thyroid & Lung (CTL) Kit • FusionPlex® Dx
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Lumakras (sotorasib)
2ms
More T cell receptors to the RAScue in cancer? (PubMed, J Clin Invest)
The TCRs were derived from healthy donors or patients with pancreatic cancer who had received a vaccine against mutant KRAS. The most promising TCRs warrant testing in patients with KRAS G12V-positive cancers.
Journal • IO biomarker
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12V • KRAS G12 • HLA-A*11
2ms
Targeting the Galectin-1/Ras Interaction for Treating Malignant Peripheral Nerve Sheath Tumors. (PubMed, Res Sq)
LLS30 effectively disrupts the Gal-1/Ras interaction, resulting in significant anti-tumor and anti-metastatic effects in MPNST models. These findings indicated that targeting Gal-1 with LLS30 offers a promising therapeutic approach for treating MPNSTs and may also be applicable to other malignancies where Gal-1 and Ras are key oncogenic drivers.
Journal
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KRAS (KRAS proto-oncogene GTPase) • NF1 (Neurofibromin 1) • LGALS1 (Galectin 1)
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KRAS G12V • HRAS G12V
2ms
Mutant KRAS in Circulating Tumor DNA as a Biomarker in Localized Pancreatic Cancer in Patients Treated with Neoadjuvant Chemotherapy. (PubMed, Ann Surg)
Throughout treatment, KRAS ctDNA is detectable by ddPCR in patients with localized PDAC treated with NAC. Detection of mutant KRAS G12V after resection was associated with reduced OS.
Journal • Circulating tumor DNA
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12V • KRAS G12
2ms
Prognostic Role of Specific KRAS Mutations Detected in Aspiration and Liquid Biopsies from Patients with Pancreatic Cancer. (PubMed, Genes (Basel))
In contrast, patients with detected KRAS G12R in the tissue survived nearly twice as long as other patients in the aggregate (286 days, 95% CI: 70-602 vs. 162 days, 95% CI: 122-600, p = 0.0374) or patients with other KRAS mutations (286 days, 95% CI: 70-602 vs. 137 days, 95% CI: 107-600, p = 0.0257). Differentiation of specific KRAS mutations in EUS-FNB and ctDNA (above all, the crucial G12D and G12R) is feasible in routine management of PDAC patients and imperative for assessment of prognosis.
Journal • Liquid biopsy • Biopsy
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12R • KRAS G12 • KRAS G12S
2ms
Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma-A New Tool for Molecular Profiling of KRAS Mutations in Tumor and Plasma Samples. (PubMed, Cancers (Basel))
ARMS-HRMA is a rapid and cost-effective method for detecting KRAS mutations in PDAC patients, offering the potential for stratifying prognosis and guiding treatment decisions. The presence of G12D and G12C mutations in both tumor and plasma is associated with a poorer prognosis.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12
2ms
Unveiling the role of KRAS in Chinese colorectal cancer patients: a positive influence on tumor mutational burden. (PubMed, Transl Cancer Res)
Increased TMB was observed in cases of KRAS and BRAF mutation combined with APC single mutation; furthermore, the expression of TMB in G12V was the highest, and G12D presented the lowest TMB in single KRAS-mutant subtypes or the combination with APC mutations. The TMB driven by KRAS co-mutations may have the potential to be used as a key biomarker for prediction of treatment outcomes of immune checkpoint inhibitors (ICIs) in patients with CRC, especially with APC co-mutation.
Journal • Tumor mutational burden • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • APC (APC Regulator Of WNT Signaling Pathway)
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TP53 mutation • KRAS mutation • BRAF mutation • KRAS G12D • KRAS G12V • APC mutation • KRAS G12
2ms
Synergistic anti-tumor activity, reduced pERK, and immuno-stimulatory cytokine profiles with 5-FU or ONC212 plus KRAS G12D inhibitor MRTX1133 in CRC and pancreatic cancer cells independent of G12D mutation. (PubMed, Am J Cancer Res)
We investigated cell viability, drug synergies, pERK suppression and cytokine, chemokine or growth factor alterations following treatment with 5-Fluorouracil (5-FU) or ONC212 plus MRTX1133 in 6 human CRC and 4 human pancreatic cancer cell lines. Our studies reveal preclinical activity of MRTX1133 alone or synergies when combined with 5-FU or ONC212 against mCRC and pancreatic cancer cells regardless of KRAS G12D mutation. The results suggest that KRAS G12V and KRAS G13D should be further considered in clinical trials including combination therapies involving MRTX1133 and 5-FU or ONC212.
Journal
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KRAS (KRAS proto-oncogene GTPase) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL18 (Interleukin 18)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS G13D • RAS wild-type • KRAS G13
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5-fluorouracil • MRTX1133 • ONC212
2ms
ADT-1004: A First-in-Class, Orally Bioavailable Selective pan-RAS Inhibitor for Pancreatic Ductal Adenocarcinoma. (PubMed, bioRxiv)
ADT-1004 demonstrated superior efficacy over sotorasib and adagrasib in tumor models involving human PDAC cells resistant to these KRAS G12C inhibitors. As a pan-RAS inhibitor, ADT-1004 has broad activity and potential efficacy advantages over allele-specific KRAS inhibitors by averting resistance. These findings support clinical trials of ADT-1004 for KRAS mutant PDAC.
Journal
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KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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KRAS mutation • KRAS G12D • KRAS G12V • RAS mutation • RAS wild-type • KRAS G13
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Lumakras (sotorasib) • Krazati (adagrasib)
3ms
BDTX-4933-101: A Study of BDTX-4933 in Patients With KRAS, BRAF and Select RAS/MAPK Mutation-Positive Cancers (clinicaltrials.gov)
P1, N=100, Active, not recruiting, Black Diamond Therapeutics, Inc. | Recruiting --> Active, not recruiting
Enrollment closed
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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KRAS mutation • KRAS G12C • BRAF mutation • NRAS mutation • KRAS G12D • KRAS G12V • KRAS G12 • NRAS G12D
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BDTX-4933
3ms
Sustained response to anti-PD-1 therapy in combination with nab-paclitaxel in metastatic testicular germ cell tumor harboring the KRAS-G12V mutation: a case report. (PubMed, Urol Int)
To the best of our knowledge, this is the first successful case of KRAS-mutation patient with TGCT who achieved partially and sustained disease remission by combining immune checkpoint inhibitors with chemotherapy. This case provides an excellent example for personalized treatment of metastatic TGCTs.
Journal • Combination therapy • PD(L)-1 Biomarker • IO biomarker • Metastases
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12V • KRAS G12
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cisplatin • albumin-bound paclitaxel
3ms
A novel platform for mutation detection in colorectal cancer using a PNA-LNA molecular switch. (PubMed, Biosens Bioelectron)
This platform is significantly faster, relatively cheaper, has superior sensitivity and specificity, and does not require any high-end equipment. To conclude, this method has the potential to be translated into clinical settings for the detection of mutations in diverse diseases and conditions.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12
3ms
Overcoming immune evasion from post-translational modification of a mutant KRAS epitope to achieve TCR-engineered T cell-mediated antitumor activity. (PubMed, bioRxiv)
Mechanistically, a gene knockout screen to identify mechanism(s) by which tumor cells methylate or demethylate this epitope unveiled SPT6 as a demethylating protein that could be targeted to improve effectiveness of these TCRs. These findings highlight the role of post-translational modifications in immune evasion and suggest that identifying and targeting such modifications should facilitate development of more effective TCR-T cell therapies.
Journal • IO biomarker
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12V • KRAS G12
3ms
Molecular Analysis of High-Grade Serous Ovarian Carcinoma Exhibiting Low-Grade Serous Carcinoma and Serous Borderline Tumor. (PubMed, Curr Issues Mol Biol)
After surgery, TC (Paclitaxel + Carbopratin) + bevacizumab therapy was administered as adjuvant chemotherapy followed by bevacizumab as maintenance therapy. DNA methylation analysis did not show differentially methylated regions. This case suggests that SBT and LGSC may transform into HGSC via p53 dysfunction due to MDM2 amplification.
Journal
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)
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TP53 mutation • TP53 wild-type • KRAS G12V • MDM2 amplification • KRAS G12 • TP53 amplification
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Avastin (bevacizumab) • paclitaxel
3ms
Temporal stability and chemotherapy responsiveness of classical and basal transcriptional subtypes of pancreatic cancer* (AACRPanCa 2024)
Initial data suggest worse outcomes to FOLFIRINOX (FFX) compared with gemcitabine nab-paclitaxel (GnP) in basal tumors... SB subtype is a strong independent predictor of worse outcomes, irrespective of mutant KRAS allele or upfront chemotherapy regimen, and tends to remain stable between biopsies in individual patients
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMAD4 (SMAD family member 4)
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TP53 mutation • KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12R • KRAS G12 • SMAD4 mutation
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PurIST℠ Test
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gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium
3ms
U2AF1 S34F enhances tumorigenic potential of lung cells by exhibiting synergy with KRAS mutation and altering response to environmental stress. (PubMed, bioRxiv)
Interestingly, HBEC3kts harboring only U2AF1 S34F display increased splicing in stress granule protein genes and viability in cigarette smoke concentrate. Our results suggest that U2AF1 S34F may potentiate transformation by granting precancerous cells survival advantage in environmental stress, permitting accumulation of additional mutations like KRAS G12V , which synergize with U2AF1 S34F to transform the cell.
Journal
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KRAS (KRAS proto-oncogene GTPase) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)
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KRAS mutation • KRAS G12V • KRAS G12 • U2AF1 mutation • U2AF1 S34F
3ms
KRAS mutations in pulmonary adenocarcinomas (ECP 2024)
KRAS is an attractive therapeutic strategy due to its high prevalence and its role in initiating and sustaining tumour growth. Approval of KRAS G12C inhibitors in locally advanced or metastatic NSCLC has brought hope to many patients. Studies show that non G12C KRAS mutation are found in 53% of adenocarcinomas.
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • GNAS (GNAS Complex Locus)
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TP53 mutation • KRAS mutation • BRAF mutation • HER-2 amplification • KRAS G12D • PTEN mutation • KRAS G12V • MET exon 14 mutation • ALK mutation • KRAS G12A • FGFR3 amplification • KRAS G13C
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Oncomine Precision Assay
3ms
Cytologic diagnosis of papillary renal neoplasm with reverse polarity. (PubMed, Cancer Cytopathol)
The cytologic features of this distinctive, indolent neoplasm are important to recognize because patients with papillary renal neoplasm with reverse polarity may be excellent candidates for partial nephrectomy or even active surveillance.
Journal
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KRAS (KRAS proto-oncogene GTPase) • GATA3 (GATA binding protein 3)
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KRAS mutation • KRAS G12V • KRAS G12
4ms
Insight into structural dynamics involved in activation mechanism of full length KRAS wild type and P-loop mutants. (PubMed, Heliyon)
Further, the Markov state modelling analysis confirmed that the mutations, especially G13D imparts rigidity to structure compared to wild type and thus limiting its conformational state in either intermediate state or active state. The study suggests that along with SW-I and SW-II regions, the loop region preceding the α3 helix and α3 helix are also involved in affecting the hydrolysis of nucleotides and may be considered while designing therapeutics against KRAS.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS wild-type • RAS wild-type
4ms
Clinical characteristics of KRAS mutation subtypes in non-small cell lung cancer population in Xinjiang, China, and their impact on the prognosis of immunotherapy. (PubMed, J Cancer Res Clin Oncol)
KRAS mutation subtypes exhibit distinct clinical and molecular characteristics and varying responses to immunotherapy. G12C and G12V mutations correlate with better immunotherapy outcomes, while G12D mutations are associated with poorer responses.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • KMT2C (Lysine Methyltransferase 2C) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1)
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PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • KRAS G12C • KRAS G12D • KRAS G12V • STK11 mutation • KRAS G12
5ms
Location of Metastases and Prognosis of Patients with Metastatic KRAS-Mutant Non-Small Cell Lung Cancer (IASLC-WCLC 2024)
Conclusions : In our cohort, KRAS -mutant patients appear to have a different metastatic pattern depending on their KRAS mutation subtype. In addition, KRAS G12C and KRAS G12V -mutant patients seem to have better prognosis and response to chemoimmunotherapy than KRAS G12D -mutant patients.
Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
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PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12 • KRAS G12C + PD-L1 expression • KRAS Q61L
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PD-L1 IHC 22C3 pharmDx • Oncomine™ Comprehensive Assay v3M • Oncomine Precision Assay
7ms
Potent antitumor activity of a bispecific T-cell engager antibody targeting the intracellular antigen KRAS G12V. (PubMed, Biomol Biomed)
HLA-G12V/CD3 BiTE in vivo testing showed delayed tumor growth without severe toxicity to major organs and prolonged mouse survival. This study highlights the potential of constructing BiTEs recognizing an HLA-peptide complex and providing a novel therapy for cancer treatment targeting the intracellular tumor antigen.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12V • KRAS G12
8ms
Myxoid Inflammatory Myofibroblastic Sarcoma: Clinicopathologic Analysis of 25 Cases of a Distinctive Sarcoma With Deceptively Bland Morphology and Aggressive Clinical Behavior. (PubMed, Am J Surg Pathol)
The patient whose tumor harbored SEC31A::PDGFRA was treated after multiple relapses with imatinib and sunitinib therapy, with progression-free periods of 5 and 2 years, respectively. Despite its bland appearance, myxoid inflammatory myofibroblastic sarcoma harbors a significant risk for disseminated disease, particularly when it occurs in the peritoneum. Targeted therapy could be considered for patients with disseminated disease.
Journal
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KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TNFRSF8 (TNF Receptor Superfamily Member 8) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • JAK1 (Janus Kinase 1) • SEC31A (SEC31 Homolog A COPII Coat Complex Component)
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KRAS mutation • ALK rearrangement • KRAS G12V • TNFRSF8 expression • KRAS G12 • KRAS Q61H
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imatinib • sunitinib
8ms
DC Vaccine in Pancreatic Cancer (clinicaltrials.gov)
P1, N=29, Completed, University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Feb 2024 | Trial primary completion date: Sep 2024 --> Feb 2024
Trial completion • Trial completion date • Trial primary completion date
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KRAS (KRAS proto-oncogene GTPase) • HLA-A (Major Histocompatibility Complex, Class I, A)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12R • HLA-A*03 • KRAS G12 • HLA-A*02 • HLA-A*11
8ms
KRAS Allelic Variants in Biliary Tract Cancers. (PubMed, JAMA Netw Open)
This cohort study found that KRAS allelic variants were relatively common and may be potentially actionable genomic alterations in patients with BTCs, especially perihilar cholangiocarcinoma and extrahepatic cholangiocarcinoma. The findings add to the growing data on genomic and immune landscapes of KRAS allelic variants in BTCs and are potentially of value to the planning of specific therapies for this heterogeneous patient group.
Retrospective data • Journal • Tumor mutational burden • MSi-H Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IFNG (Interferon, gamma)
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KRAS mutation • MSI-H/dMMR • NRAS mutation • KRAS G12D • KRAS G12V • TMB-L • KRAS G12 • NRAS Q61 • KRAS Q61H • NRAS G12D
8ms
Oncogenic Kras induces spatiotemporally specific tissue deformation through converting pulsatile into sustained ERK activation. (PubMed, Nat Cell Biol)
Using a reporter mouse capture real-time ERK signal dynamics at the single-cell level, we discovered that KrasG12D, but not a closely related mutation HrasG12V, converts ERK signal in stem cells from pulsatile to sustained. Finally, we demonstrated that interrupting sustained ERK signal reverts KrasG12D-induced tissue deformation through modulating specific features of cell migration and division.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12D • KRAS G12V • HRAS mutation • KRAS G12 • NRAS G12 • HRAS G12V
8ms
Clinical and genomic landscape of RAS mutations in gynecologic cancers. (PubMed, Clin Cancer Res)
RAS mutations in gynecologic cancers have a distinct histopathologic distribution and may impact overall survival. PIK3CA, PTEN, and ARID1A are potentially actionable co-alterations. RAS pathway-targeted therapy should be considered.
Journal
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • RAS (Rat Sarcoma Virus)
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TP53 mutation • KRAS mutation • NRAS mutation • PIK3CA mutation • KRAS G12D • PTEN mutation • ARID1A mutation • KRAS G12V • RAS mutation • KRAS G12 • NRAS G12D • NRAS G12
8ms
Targeting KRAS in pancreatic cancer. (PubMed, Oncol Res)
However, the most common KRAS mutations in PDAC are G12D (44%), G12V (34%) and G12R (20%) that are not amenable to treatment by KRAS G12C-directed cysteine-reactive KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung cancer...Recently, the KRAS G12D-directed MRTX1133 inhibitor has entered clinical trials and more of such inhibitors are in development. The other KRAS mutations may be targeted indirectly via inhibition of the cognate guanosine exchange factor (GEF) Son of Sevenless 1 that drives KRAS. These agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes.
Review • Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V
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Lumakras (sotorasib) • Krazati (adagrasib) • MRTX1133
8ms
Identification and affinity enhancement of T-cell receptor targeting a KRASG12V cancer neoantigen. (PubMed, Commun Biol)
This high-affinity TCR mutant, which involved only two amino acid substitutions, display minimal conformational alterations while maintaining a high degree of specificity for the KRASG12V peptide. Our research unveils the molecular mechanisms governing TCR recognition towards KRASG12V neoantigen and yields a range of affinity-enhanced TCR mutants with significant potential for immunotherapy strategies targeting tumors harboring the KRASG12V mutation.
Journal • IO biomarker
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12V • KRAS G12 • HLA-A*11
8ms
Pneumonic-type lung adenocarcinoma with KRAS G12V mutation and sustained response to Afatinib. (PubMed, Pneumonia (Nathan))
Our case highlights the typical and dynamic changes in imaging features of P-ADC and provides an indicative treatment strategy for KRAS G12V-mutated lung adenocarcinoma.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12V • KRAS G12
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Gilotrif (afatinib)
8ms
Targeting KRAS Diversity: Covalent Modulation of G12X and Beyond in Cancer Therapy. (PubMed, J Med Chem)
This breakthrough led to the development and approval of sotorasib (AMG510) and adagrasib (MRTX849), revolutionizing the treatment of KRASG12C-dependent lung cancer. Insights from successful KRASG12C targeting informed the design of molecules addressing other mutations, often in a covalent manner. These findings offer promise for innovative approaches in addressing commonly occurring KRAS mutations such as G12D, G12V, G12A, G12S, and G12R in various cancers.
Review • Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • RAS mutation • KRAS G12A • KRAS G12 • KRAS G12S
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Lumakras (sotorasib) • Krazati (adagrasib)
8ms
Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases. (PubMed, ESMO Open)
In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS G12R • KRAS G12A • KRAS G12 • KRAS G12S • KRAS Q61H • KRAS A146T • KRAS A146V • KRAS G13A • KRAS G13C
9ms
The Clinical Implications of KRAS Mutations and Variant Allele Frequencies in Pancreatic Ductal Adenocarcinoma. (PubMed, J Clin Med)
Furthermore, novel technologies and therapies are being developed to target specific mutant subtypes, with encouraging early results. In this paper, we aim to review the recent studies regarding the relative impact of specific mutant KRAS subtypes on oncologic outcomes, the application of variant allele frequency in next generation sequencing analyses, and the ongoing research into therapies targeting specific mutant KRAS subtypes.
Review • Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12 • KRAS Q61H
9ms
A Facile Method to Append a Bio-ID Tag to Endogenous Mutant Kras Alleles. (PubMed, Methods Mol Biol)
These proteins are captured through the strong interaction between the biotin label and streptavidin bead and subsequently identified by mass spectrometry. Here, we developed a protocol using CRISPR-mediated gene editing to generate endogenous BioID2-tagged KrasG12D and KrasG12V isogenic murine colon epithelial cell lines to identify unique protein proximity partners by BioID.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12 • KRAS A146 • KRAS Q61
9ms
Radiological and clinical features of large consolidative-type pulmonary invasive mucinous adenocarcinoma. (PubMed, Clin Respir J)
Halo, vacuole, angiogram, and dead branch signs were frequently observed in consolidative-type IMA. Kirsten rat sarcoma viral oncogene mutations are common in consolidative-type IMA, especially site G12V, whereas epidermal growth factor receptor mutations were rare; therefore, gene immunotherapy was more difficult. Most patients were in stage T3-T4; however, lymph node metastasis was rare.
Retrospective data • Journal • IO biomarker
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • EGFR mutation • KRAS G12V • KRAS G12
9ms
Aberrant Glycosylation in Pancreatic Ductal Adenocarcinoma 3D Organoids Is Mediated by KRAS Mutations. (PubMed, J Oncol)
Meanwhile, mannose-binding lectin (rRSL [Ralstonia solanacearum] and rBC2LA [Burkholderia cenocepacia]) signals were higher while those of galactose-binding lectins (rGal3C and rCGL2) were lower in the KRAS mutants. We demonstrated here that PDAC 3D-cultured organoids with KRAS mutations were dominantly covered in increased fucosylated glycans, pointing towards novel treatment targets and/or tumor markers.
Journal
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KRAS (KRAS proto-oncogene GTPase) • FUT3 (Fucosyltransferase 3)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS wild-type • RAS wild-type • KRAS G12 • KRAS Q61L • KRAS expression
9ms
Prognostic value of KRAS G12V mutation in lung adenocarcinoma stratified by stages and radiological features. (PubMed, J Thorac Cardiovasc Surg)
KRAS G12V mutation was associated with aggressive clinical-pathological phenotype and early recurrence. To note, this mutation exhibited significantly worse prognosis in part-solid and stage Ⅰ lung adenocarcinoma patients. Meanwhile, the prognostic significance of KRAS G12C and G12V variants were comparable.
Journal • PD(L)-1 Biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • KDR (Kinase insert domain receptor) • FGF3 (Fibroblast growth factor 3)
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PD-L1 expression • KRAS mutation • KRAS G12C • KRAS G12V • RET mutation • KRAS G12
9ms
Farnesyltransferase inhibitors have antitumoral effects in mutant KRAS containing cancer cells in preclinical models (PubMed, Magy Onkol)
Accordingly, we have tested FTIs (tipifarnib and lonafarnib) in G12C mutant human cancer cell lines in vitro and in vivo. At last, we have also tested FTIs on G12V mutant human cancer cells and again we have detected antitumoral effects. We suggest that FTIs may have clinical relevance outside the HRAS mutant cancers.
Preclinical • Journal
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KRAS (KRAS proto-oncogene GTPase) • HRAS (Harvey rat sarcoma viral oncogene homolog)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • HRAS mutation • HRAS G12C
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Zarnestra (tipifarnib)